Systemic lupus erythematosus: lupus nephritis

Overview

General background | Focus of the review | Comments on evidence | Search and appraisal summary | Substantive changes at this update | Abstract | Cite as

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General background

Lupus nephritis occurs in around a third of patients with systemic lupus erythematosus (SLE) and is more common in men with SLE than women. The risk of end-stage renal disease (ESRD) is higher in non-white people, especially in those of black ethnicity, in those over the age of 30 years, and if hypertension is present. Immuosuppressants are used with corticosteroids to improve renal outcomes in patients with proliferative nephritis, but even with treatment, up to 25% of patients progress to develop renal insufficiency and ESRD. The use of immunosuppressants can be limited by bone marrow toxicity, the risk of gonadal failure, and infections.

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Focus of the review

Evidence that mycophenolate can substitute for cyclophosphamide in the management of proliferative lupus nephritis has resulted in further investigation of the potential benefits, as well as risks. Other immunosuppressants have also been evaluated to show their equivalence/superiority to standard immunosuppressive treatments. For this overview, we have focused on for studies that compared cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, or abatacept with corticosteroid, or with each other. Other treatments are available, including rituximab, but these were outside of our scope for this focused overview.

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Comments on evidence

Several high-quality RCTs have been undertaken to investigate the benefits and risks of single immunosuppressants as adjuncts to corticosteroid therapy in people with proliferative nephritis. The use of immunosuppressants can be limited by bone marrow toxicity, the risk of gonadal failure, and infections.

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Search and appraisal summary

The update literature search for this overview was carried out from the date of the last search, December 2007, to April 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. At this update, searching of electronic databases retrieved 448 studies. After deduplication and removal of conference abstracts, 120 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 53 studies and the further review of 67 full publications. Of the 67 full articles evaluated, four systematic reviews and one RCT were added at this update.

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Substantive changes at this update

Cyclophosphamide plus corticosteroid compared with corticosteroid alone New option. One systematic review added.[14] Categorised as 'trade-off between benefits and harms'.

Azathioprine plus corticosteroid compared with corticosteroid alone New option. One systematic review added.[14] Categorised as 'trade-off between benefits and harms'.

Mycophenolate mofetil plus corticosteroid compared with corticosteroid alone New option. We found no systematic reviews or RCTs. Categorised as 'unknown effectiveness'.

Tacrolimus plus corticosteroid compared with corticosteroid alone New option. We found no systematic reviews or RCTs. Categorised as 'unknown effectiveness'.

Abatacept plus corticosteroid compared with corticosteroid alone New option. We found no systematic reviews or RCTs. Categorised as 'unknown effectiveness'.

Mycophenolate mofetil plus corticosteroid compared with cyclophosphamide plus corticosteroid New option. Three systematic reviews added.[14][15][16] Categorised as 'trade-off between benefits and harms'.

Mycophenolate mofetil plus corticosteroid compared with tacrolimus plus corticosteroid New option. One systematic review added.[14] Categorised as 'trade-off between benefits and harms'.

Cyclophosphamide plus corticosteroid compared with azathioprine plus corticosteroid New option. One systematic review added.[14] Categorised as 'trade-off between benefits and harms'.

Cyclophosphamide plus corticosteroid compared with tacrolimus plus corticosteroid New option. Two systematic reviews added.[14][18] Categorised as 'trade-off between benefits and harms'.

Tacrolimus plus corticosteroid compared with azathioprine plus corticosteroid New option. One RCT added.[19] Categorised as 'trade-off between benefits and harms'.

Abstract

INTRODUCTION: Systemic lupus erythematosus (SLE) occurs predominantly in young women, but also in children. The prevalence of SLE varies worldwide, ranging from about 1 in 3500 women (regardless of race) in the UK, to 1 in 1000 women in China, to 1 in 250 African-American women in the US. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of immunosuppressants in people with proliferative lupus nephritis? What are the effects of different immunosuppressants compared with each other in people with proliferative lupus nephritis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 448 studies. After deduplication and removal of conference abstracts, 120 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 53 studies and the further review of 67 full publications. Of the 67 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for 13 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 10 interventions based on the effectiveness and safety of immunosuppressants plus corticosteroids compared with corticosteroids alone, and immunosuppressants plus corticosteroids compared with each other in people with proliferative lupus nephritis (WHO grades III–V).

Cite as

Madhok R. Systemic lupus erythematosus: lupus nephritis. Systematic review 1123. BMJ Clinical Evidence. . 2015 December. Accessed [date].

Latest citations

Treatments for Lupus Nephritis: A Systematic Review and Network Metaanalysis. ( 10 January 2017 )

Risk of Serious Infection for Patients with Systemic Lupus Erythematosus Starting Glucocorticoids with or without Antimalarials. ( 10 January 2017 )